The purpose of these studies is to investigate the mechanism by which somatomedins stimulate cell division and to relate these findings to processes occurring in transformed cells. The IGFs elicit their biological effect by binding to specific cell membrane receptors. Two physicochemically distinct IGF receptors, termed the type I and type II IGF receptors, have been identified. While evidence indicates that the type I is involved in the regulation of cell division, it is not known if the type II receptor also mediates this response. The first aim of these studies is to define the roles of these two IGF receptor types in mediating the cellular proliferative response. The second aim of these studies is to characterize specific intracellular events induced by the IGF and to relate these to the mechanism of hormone action. The effects of the IGFs on selective protein synthesis and tyrosine-specific protein phosphorylation will be investigated. A number of alterations in the IGF pathway could result in a loss of normal growth control and contribute to the abnormal growth of transformed cells. The third aim of these studies is to determine if specific forms of cellular transformation are related to specific alterations in the IGF pathway and to investigate the effects of inhibiting this pathway on the growth of transformed cells. The information gained from these studies may lead to a better understanding of the mechanisms by which cell division is regulated and how this is modified in cancer cells. Such information could be valuable for designing new approches for diagnosing and treating of specific cancer in humans. (J)